First Patient Enrolled in Phase 2 Study of Olatec's NLRP3 Inhibitor for Type 2 Diabetes

In Basel, Switzerland, a groundbreaking clinical trial named DAPAN-DIA has commenced, enrolling its first patient with Type 2 Diabetes Mellitus (T2D) and diabetes-related complications. The study, sponsored by Principal Investigator Marc Donath MD, aims to evaluate the efficacy and safety of Olatec's NLRP3 inhibitor, dapansutrile. This Phase 2 randomized study will involve approximately 300 patients who have elevated blood glucose levels, systemic inflammation, and are at risk for diabetes complications despite receiving standard anti-diabetic therapy.

DAPAN-DIA stands out as the first clinical trial targeting T2D using a selective NLRP3 inhibitor. Unlike traditional treatments that primarily focus on lowering blood sugar, this trial will also assess cardiometabolic and other risk factors, including weight reduction when combined with GLP-1 therapy. The study is funded by a consortium that includes Olatec, the European Union under the Horizon Europe Programme, and the Swiss Government as part of the INTERCEPT-T2D initiative.

The trial is being conducted in collaboration with the University Hospital of Basel in Switzerland, under the guidance of Dr. Marc Donath, a leading researcher in immuno-metabolism. This randomized, double-blind, placebo-controlled multi-center trial will focus on patients who present with low-grade inflammation, obesity, and inadequately controlled glycemia despite standard anti-diabetic treatments. Over six months, patients will receive either dapansutrile or a placebo. Mustafa Noor MD, Chief Medical Officer at Olatec, expressed optimism that the data from this trial, especially in combination with GLP-1 therapy, will be crucial in understanding the full potential of anti-inflammatory interventions with an NLRP3 inhibitor.

The trial is set to expand beyond Swiss sites to include esteemed medical and scientific diabetes centers across Europe, such as Hôpital Lariboisière, Hôpital Bichat-Claude Bernard, and Hôpital Cochin in Paris, France; the German Diabetes Center in Düsseldorf, Germany; and the University Hospital of Liège in Belgium. Funding is secured through the INTERCEPT-T2D initiative by the European Union's Horizon Europe Programme and the Swiss Government.

T2D is a chronic condition marked by high blood glucose levels due to insulin resistance and insufficient insulin secretion. This disease is often linked with obesity and a range of complications including cardiovascular disease, kidney dysfunction, retinopathy, neuropathy, and non-alcoholic steatohepatitis. Chronic, low-grade systemic inflammation, along with NLRP3 activation and IL-1β upregulation, are observed in T2D patients. Unlike existing diabetic treatments that primarily focus on glucose reduction, dapansutrile aims at modifying the disease course by targeting the underlying NLRP3 inflammation pathway, which is implicated in insulin resistance, weight gain, and heightened cardiometabolic risks.

Dr. Donath emphasized the urgent need for effective T2D treatments that extend beyond glycemic control to address the inflammatory aspects of the disease and its cardiometabolic complications. He believes that the DAPAN-DIA Study could represent a significant advancement in managing T2D. Olatec's Founder and CEO, Damaris Skouras, highlighted that the DAPAN-DIA Study builds on previous data in heart failure and gout, marking a significant milestone in developing dapansutrile for interrelated cardiometabolic diseases linked by chronic low-grade inflammation due to NLRP3/IL-1 activation.

Type 2 diabetes is a serious, chronic condition resulting from elevated blood glucose levels due to the body's inability to produce or use insulin effectively. This leads to high blood sugar levels, which can cause damage to multiple organs, resulting in severe health complications. Life expectancy for T2D patients is typically reduced by approximately eight years, with a significant increase in mortality and morbidity risks. As the prevalence of T2D continues to rise globally, the economic burden on healthcare systems is also escalating, with substantial increases in healthcare expenditures attributed to T2D.

The scientific rationale behind targeting the NLRP3 inflammasome in T2D is based on its central role in orchestrating inflammation and immune responses in response to metabolic signals, leading to insulin resistance, pancreatic β-cell failure, and other complications. Antagonizing the IL-1 pathways has shown potential in preventing β-cell dysfunction, improving glycemia, and reducing cardiovascular complications. Thus, targeting this pathway offers numerous therapeutic advantages over current treatments for T2D.